eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Thyroid, Medullary Carcinoma

Author: Anastasios K Konstantakos, MD, Clinical Associate Surgeon, Department of Cardiovascular Surgery, Billings Clinic, Billings, Montana
Contributor Information and Disclosures

Updated: Sep 29, 2009

Introduction

Background

Medullary carcinoma of the thyroid (MTC) is a distinct thyroid carcinoma that originates in the parafollicular C cells of the thyroid gland. These C cells produce calcitonin.

Sporadic, or isolated, MTC accounts for 75% of cases, and inherited MTC constitutes the rest. Inherited MTC occurs in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, but non-MEN familial MTC also occur.

Outcome depends on extent of disease, nature of tumor biology, and overall efficacy of surgical treatment.

Advances in genetic testing in have revolutionized the management of this disease.

Pathophysiology

Medullary thyroid cancer (MTC) is usually diagnosed on physical examination as a solitary neck nodule, and early spread to regional lymph nodes is common. Distant metastases occur in the liver, lung, bone, and brain.

Sporadic MTC usually is unilateral. In association with multiple endocrine neoplasia (MEN) syndromes, it is always bilateral and multicentric. MTC typically is the first abnormality observed in both MEN 2A and 2B syndromes.

In addition to producing calcitonin, MTC cells can produce several other hormones, including corticotropin, serotonin, melanin, and prostaglandins; moreover, paraneoplastic syndromes (eg, carcinoid syndrome, Cushing syndrome) can occur in these patients.

Mutations in the RET (REarranged during Transfection) proto-oncogene, a receptor protein tyrosine kinase encoded on chromosome 10, have been classified into discrete subtypes, which confer varying degrees of risk1 ; prophylactic thyroidectomy can now be offered to specific types of patients with this genetic abnormality (see Prevention).

Frequency

United States

Medullary carcinoma of the thyroid (MTC) constitutes approximately 4% of all thyroid cancers in the United States.2 This figure translates into approximately 1000 diagnoses per year.

International

The international incidence of medullary carcinoma of the thyroid is similar to that in the United States.

Mortality/Morbidity

Isolated medullary carcinoma of the thyroid (MTC) typically demonstrates a relatively indolent biologic progression. While regional lymph node metastases are possible, the lesion may not spread outside of the cervical region until several months later. MTC associated with multiple endocrine neoplasia (MEN) syndromes may have a more aggressive course, which also depends on associated comorbidity (eg, pheochromocytoma).

Despite advances in genetic screening for the RET proto-oncogene, preliminary population studies have yet to show a definitive impact on disease prognosis.3

Age

Peak incidence of isolated medullary carcinoma of the thyroid (MTC) occurs in the fifth or sixth decade of life, and the peak incidence of MTC associated with multiple endocrine neoplasia (MEN) 2A or 2B occurs during the second or third decade of life.

Clinical

History

A specific constellation of symptoms of medullary thyroid carcinoma (MTC) is not usually noted; however, one or more of the following symptoms may be observed:

  • Patients may describe a lump at the base of the neck, which may interfere with or become more prominent during swallowing.
  • Patients with locally advanced disease may present with hoarseness, dysphagia, and respiratory difficulty.
  • Although uncommon, patients may present with various paraneoplastic syndromes, including Cushing or carcinoid syndrome.
  • Diarrhea may occur from increased intestinal electrolyte secretion secondary to high plasma calcitonin levels.
  • Distant metastases (eg, lung, liver, bone) may produce symptoms of weight loss, lethargy, and bone pain.

Physical

  • Physical examination may demonstrate a dominant thyroid nodule at the base of the neck.
  • Palpable cervical lymphadenopathy signifies disease that has progressed locally.
  • Abdominal pain, jaundice, and rarely, bone tenderness may occur in patients with systemic metastases.

Causes

  • Medullary carcinoma of the thyroid (MTC) has a genetic association with multiple endocrine neoplasia (MEN) 2A and 2B; however, it is heritable by a non-MEN mode of transmission. Sporadic MTC occurs in 75% of patients, and familial MTC constitutes the other 25%.
  • Mutations in RET can lead to MTC development in cells derived from neural crest tissue.

More on Thyroid, Medullary Carcinoma

Overview: Thyroid, Medullary Carcinoma
Differential Diagnoses & Workup: Thyroid, Medullary Carcinoma
Treatment & Medication: Thyroid, Medullary Carcinoma
Follow-up: Thyroid, Medullary Carcinoma
References
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References

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Further Reading

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Keywords

medullary thyroid carcinoma, MTC, thyroid cancer, thyroid cancer symptoms, thyroid cancer diagnosis, thyroid cancer treatment, thyroid tumor, multiple endocrine neoplasia, MEN, thyroidectomy, hypothyroidism

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Contributor Information and Disclosures

Author

Anastasios K Konstantakos, MD, Clinical Associate Surgeon, Department of Cardiovascular Surgery, Billings Clinic, Billings, Montana
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

 
 
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